The primary aim of this study is to ascertain whether UA directly stimulates a pro-inflammatory response. Secondary aims are to document thee effect of higher versus lower UA levels on circulating antioxidant biomarkers, endothelium function, clinical and laboratory parameters.[unreadable] Both primary and secondary aims will be tested using two different trials whose results will be complementary. [unreadable] In the first study (Cohort#1): Uric Acid versus Placebo Trial, the primary and secondary outcomes will be estimated after raising the circulating UA levels by systemic UA infusion.[unreadable] In the second study (Cohort#2): Rasburicase versus Placebo Trial, the primary and secondary outcomes will be estimated after lowering the circulating UA levels by systemic infusion of Rasburicase, a recombinant urate oxidase. [unreadable] In both Trials, the primary and secondary outcomes will be evaluated before and after intervention and comparisons between intervention and placebo groups will be also estimated.[unreadable] [unreadable] Testing treatments causing opposite change of circulating UA levels is based is the only approach that can shed light on whether UA is a causal, compensatory or co-incidental factor associated with modification of the inflammatory status. [unreadable] In the Cohort#1: Uric Acid versus Placebo Trial, UA systemic infusion will rapidly increase the circulating UA levels. We expect that the sudden increase of circulating UA levels may directly affect circulating levels of cytokines, antioxidant biomarkers and other outcome parameters. [unreadable] In the Cohort#2: Rasburicase versus Placebo Trial, Rasburicase systemic administration will rapidly lower the circulating UA levels without restoration of them within few days from the infusion. We expect that a sudden decrease of circulating UA levels may affect circulating cytokines, antioxidant biomarkers and all other outcomes with an opposite fashion compared to Cohort#1: Uric Acid versus Placebo Trial. [unreadable] [unreadable] Both short term approaches of Cohort#1: Uric Acid versus Placebo Trial and Cohort#2: Rasburicase versus Placebo Trial are more likely to allow a better understanding of the possible mechanisms that link raised circulating UA levels and increased cardiovascular risk that observational and epidemiological data are unlikely to resolve. Additionally, this would be a valid approach in healthy individuals as suggested by studies exploring the effect of sudden changes of cardiovascular risk factors, such as saturated fats or circulating homocysteine concentrations, on biological and instrumental parameters (33, 34).[unreadable] [unreadable] Study Design[unreadable] This is a prospective placebo-controlled overall 2-months study which consists of two trials, Cohort#1: Uric Acid versus Placebo and Cohort#2: Rasburicase versus Placebo respectively. Participants will be community-dwelling women and men, aged 50-70 years and having BMI within 23-30. All participants must be capable of attending an outpatient setting at the required protocol time-points. [unreadable] [unreadable] The first criteria according to participants will be allocated to Cohort#1: Uric Acid versus Placebo or Cohort#2: Rasburicase versus Placebo will be the UA circulating levels. Participants with Uric Acid < 6mg/dl will be allocated to Cohort#1: Uric Acid versus Placebo, while participants with Uric Acid >7 mg/dl will be allocated to Cohort#2: Rasburicase versus Placebo. [unreadable] [unreadable] The choice of a Uric Acid threshold is relevant because of (1) the characteristics of the treatment (UA will increase, while Rasburicase will decrease UA plasma levels), (2) the target of the study which is to dissect out whether lowering or increasing the UA levels may affect cytokines and antioxidant parameters, and (3) the scant number of total participants. However, to be finally enrolled in each cohort, participants have to satisfy specific inclusion/exclusion criteria which are explained in details in the remaining of this document.[unreadable] [unreadable] According to the sequence of presentation of participants who will result eligible to the Cohort#1 or Cohort#2, they will be blocked according sex and each subject will be randomly assigned to treatment or placebo up to reach 5 groups of two subjects (1 intervention and 1 control subject) in each cohort (see the follow Enrollment schema).[unreadable] [unreadable] The randomization list will be maintained by the protocol study monitor. Two sealed copies of the randomization list will be stored at the NIA; one with the PI and one secured in the NIA/MRI Research Pharmacy. Medications will be dispensed to subjects from the NIA Research Pharmacy. The P.I. or designated NIA physician will review the laboratory results with the identity of the subject kept anonymous. [unreadable] [unreadable] Cohort#1: Uric Acid versus placebo[unreadable] Twenty participants will be enrolled in this cohort, 10 men and 10 women respectively. In each sex group, 5 individuals will be randomly assigned to intervention and 5 to placebo treatment. All participants should have Uric Acid< 6 mg/dl. [unreadable] [unreadable] Cohort#2: Rasburicase versus placebo[unreadable] Twenty participants will be enrolled in this cohort, 10 men and 10 women. In each sex group, 5 individuals will be randomly assigned to intervention and 5 to placebo traetment. All participants should have Uric Acid>7 mg/dl.[unreadable] [unreadable] In both trials, participants will be asked to complete screening on visit 1. A physician will review participants. study eligibility on visit 2, and the randomization list of eligible participants will be also generated on visit 2. Baseline evaluations and interventions (i.e. treatment or placebo, respectively) will be performed on visit 3 under physician.s control. During visit 3 participants in Cohort#1: Uric Acid versus placebo trial will be evaluated at 1 hour, 2 hours, 4 hours, 8 hours, 12 hours and 24 hours after intervention. During visit 3 participants in Cohort#2: Rasburicase versus placebo trial will be evaluated at 4 hours, 8 hours, 12 hours and 24 hours after intervention. To guarantee similar baseline conditions and exclude the influence of external stress on changes in biological parameters, participants will be asked to spend in the internal ward the night before treatment. To estimate the short-term effects of the intervention by biological parameters and instrumental evaluations, and to check on the onset of side effects in the first 24 hours, participants will be asked to spend the night after the intervention at the Harbor Hospital. The long-term effect will be evaluated at visit 4 and visit 5 that will be scheduled at 48 hours and 2 weeks from treatment, respectively.[unreadable] [unreadable] Since Uric Acid is not currently an FDA approved drug from any indication, an IND has been submitted to the FDA. Although the application was considered positively, additional information on sterility, solubility and concentration of endotoxins in the final product were requested. Additional testing is currently conducted to address the questions posed by the FDA.